Center Project Summary/Abstract This is an application for renewal of the George M. O'Brien Kidney Center at Yale. This center was established with the overarching goal to facilitate basic, translational and clinical research that will advance the prevention and treatment of kidney diseases. Major research areas of emphasis are epithelial cell biology and renal physiology; inherited kidney disease and kidney development; acute kidney injury (AKI) and chronic kidney disease (CKD); and vascular biology, inflammation and glomerular disease. A critically important benefit of the Center is to provide renal investigators both at Yale and across the country with access to highly specialized services not otherwise routinely available to support their research. To this end, the Center includes three Biomedical Research Cores. The Animal Physiology and Phenotyping Core (Core A) provides specialized services and training for assessing renal function and blood pressure regulation in small animals. Its services include clearance studies in anesthetized animals, perfusion fixation for histology studies, serum and urine electrolyte values, acid-base parameters, serum and urine creatinine, balance studies in metabolic cages, acute blood pressure measurements in anesthetized mice, and chronic awake blood pressure measurements by radiotelemetry. The Disease Models and Mechanisms Core (Core B) provides users with ready access to unique mouse models, associated cell line resources, and advanced human translational technologies. Its services include bacterial artificial chromosome (BAC) recombineering and transgenesis, support for CRISPR/Cas9 genome editing for mouse line production, support for kidney cell line production by genome editing or from mutant mice, and support for targeted protein-based interrogation of human urine and kidney biopsy samples. The Human Genetics and Clinical Research Core (Core C) provides services and training to enhance translational studies in kidney disease. Initially established to facilitate genetics studies, its services include patient DNA extraction and archiving, tools for high throughput SNP genotyping and DNA sequencing, analysis of genetic linkage and linkage disequilibrium, and whole exome capture and sequencing. Its services have been expanded to now facilitate translational research beyond genetics, including support for protocol development, patient recruitment, sample processing, biobanking, multiplex assays for biomarkers, and biostatistical and epidemiological support. Our cores currently have a combined user base of >145 investigators, including >90 at outside institutions. A Pilot and Feasibility Program has the goals of providing initial project funding for young investigators, attracting new investigators into the field of kidney disease research, and fostering translational and clinical studies directly related to kidney diseases. In addition, an Enrichment Program enhances kidney disease research by maximizing interaction and information sharing among renal investigators and trainees, and by providing activities to enhance recruitment and education of all levels of trainees from undergraduate students to postdoctoral fellows.